GB1564981A - Continuous calibration system and method for analytical instruments - Google Patents

Description

PATENT SPECIFICATION

( 21) Application No 1761/77 ( 22) Filed 17 Jan 1977 ( 31) Convention Application No 670184 ( 32) Filed 25 March 1976 in ( 33) United States of America (US) ( 44) Complete Specification published 16 April 1980 ( 51) INT CL 3 G Ol D 18/00 ( 52) Index at acceptance GIN 19 X 1 25 D 10 25 D 2 25 DX 25 E 1 BKT ( 1) 1 564 981 ( 19) ( 54) CONTINUOUS CALIBRATION SYSTEM AND METHOD FOR ANALYTICAL INSTRUMENTS ( 71) We, INSTRUMENTATION LABORATORY INC, of 113 Hartwell Avenue, Lexington, Massachusetts, United States of America; a corporation organized and existing under the laws of the State of Massachusetts, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in

and by the following statement:-

This invention relates to an analytical instrument and more particularly to an automatic continuous calibration system and fault detection method for use in such instruments Such instruments are wellknown for the analysis of parameters of precious fluids such as blood and also for parameters of constituents of our environment, whether it be in the streets, in a coal mine, on a submarine or the like.

Such analytical instruments include sensor means which are and of necessity have to be extremely sensitive to detect even the smallest required quantity of consituents in the fluid under investigation.

Therefore, they must be precisely calibrated so as to give true and accurate readings of these constituents This is particularly true since such information is frequently required for diagnostic purposes or in controlling life support means in the critically injured.

One kind of such analytical instrument for the measurement of gaseous constituents of a sample of blood is described in detail in U S Patent No.

3,672,843 entitled "Fluid Analyzing Apparatus," filed in the name of Thomas A.

Rosse et al and assigned to the same assignee as this application and, also in U S.

Patent No 3,694,734 entitled "Sensor Instrumentation," filed in the name of David E Blackmer and assigned to the same assignee as this application The disclosures of these two patents are incorporated herein by reference and, as will be more fully described below, the system of the present invention is fully compatible with and connectable to the apparatus disclosed in these patents.

In addition to an extremely sensitive sensor, some of which may be covered by a selectively permeable membrane depending upon the particular constituent to be analyzed, such analytical instruments include circuitry for producing an electrical signal that is representative of the particular constituent sensed by the sensor and also include an analog-to-digital converter to allow the ready display of such signal in easily readable digital form so as to be immediately available to an attending physician.

Because of the requirements for speed and accuracy in having such diagnostic information, it is most desirable, if not required, to have such analytical instruments in perfect calibrating condition immediately before a sample is presented to the instrument for analysis Presently most analytical instruments do, of course, include calibration techniques which may vary from a manually adjustable calibration system as disclosed in the above mentioned Patents 3,672,843; 3,694,734 to more automatic systems which include techniques which periodically and automatically calibrate such instruments in certain time intervals, say 30 minutes to 2 hours or that calibrate them on command by the operator.

Since the ideal situation is to have such an instrument constantly maintained in immediate operating condition so that a sample may be presented to it almost at any time without requiring the operator to consider whether or not the instrument is properly calibrated, it is most desirable to have a system that so maintains such analytical instruments in perfect calibration at all times, automatically and without operator intervention Operator intervention need only be required where the continuous calibration system is unable for one reason or another to calibrate the instrument In that case, the instrument is preferably rendered inoperative so as to warn the operator that his intervention is 1,564,981 required before the presentation of the sample.

Accordingly, it is an object of this invention to provide a continuous automatic calibration system and fault detection method for analytical instruments of the kind used for measuring constituents of a fluid sample More specifically, it is the object of this invention to provide a continuous automatic calibration system and fault detection method which is capable to correct for certain slow response characteristics inherent in such instruments, to correct for minor system noises and shifts in readings occasioned by small variations in either the sensor, the circuitry or the readout means and, which will indicate instrument malfunction where it cannot correct the errors so as to warn the operator, requiring his intervention.

According to the present invention there is provided an analytical instrument for measuring constituents of a fluid sample, comprising, at least one sensor means, first circuitry producing a signal representative of the constituent sensed by said sensor and including an analog-to-digital converter for converting said signal to digital form for display, and means for providing continuous calibration of the instrument except when sampling by means of a second circuitry including, a comparator circuit continuously comparing the output signal of said analog-to-digital converter to a reference signal and producing an output signal representative of the difference resulting from said comparison, and an RC integrator-and-hold circuit connected to the output of said comparator circuit and producing in turn a compensatory voltage coupled to said first circuitry.

Also in accordance with the invention there is provided a method of calibrating with calibrating fluid an analytical instrument useful for measuring constituents of a fluid sample and having circuitry for producing and displaying a signal representative of such constituents, comprising, continuously comparing, except when sampling, the output of said instrument to a reference signal, applying the difference resulting from said comparison to charge or discharge an RC integrator-and-hold circuit, and coupling the resultant output from said integratorand-hold circuit to said instrument circuitry continuously to adjust its signal output.

Further in accordance with the invention there is provided a method of maintaining an analytical instrument useful for measuring constituents of a fluid and having circuitry for producing and displaying a signal representative of such constituents constantly in immediate operating condition comprising measuring continuously, except when sampling, calibration standards, comparing continuously, except when sampling, the output of said instrument to a reference signal, applying continuously the difference between said output and said reference signal to charge or discharge an RC integrator-and-hold circuit, coupling continuously, the output of said integratorand-hold circuit to said instrument circuitry continuously to correct its signal display, and producing an error signal for warning an operator when said difference between said output and said reference signal is beyond the capability of said integratorand-hold circuit to correct.

Should the above described continuous automatic calibration system not be able to correct for errors in the readout of the analytical instrument within a given period of time, either because it represents a major system breakdown or is beyond the capabilities of the system to correct, then a suitable error display means is provided, also receiving a signal from the comparator circuit This error display means will inhibit use of the analytical instrument and will warn the operator by some suitable means, such as flashing display, that his intervention in correcting the instrument is required before sampling.

Thus, the present invention provides a simple, relatively inexpensive means for continuously and automatically calibrating analytical instruments and for indicating instrument malfunctions without any further specific circuitry The result is the availability of such analytical instruments in immediate operating condition ready to receive samples to be analyzed to operating personnel at all times.

The invention will be further illustrated by way of example with reference to the accompanying drawings, in which:

Fig 1 is a block diagram of a continuous automatic calibration system as it may be incorporated in and applied to a specific blood gas instrument for measuring p H, PCO 2 and PO 2 values of blood specimens, Fig 2 a is a schematic diagram of the sample-and-hold circuit shown in Fig 1, and showing the same in more detail, Fig 2 b is a table giving the various representative values for the operative components of the sample-and-hold circuit, depending whether the same is used in the p H or the PCO 2 or the PO 2 channel, and Fig 3 depicts the timing diagram for the continuous automatic calibration system of the invention.

With reference to Fig 1, there is shown in block diagram a particular embodiment of the continuous automatic calibration system of the invention as it has been incorporated into a specific blood gas instrument made by 1,564,981 the assignee of this application and, as more specifically shown and described in U S.

Patent No 3,672,843 This particular blood gas instrument is a three channel analytical instrument designed to measure the p H, PCO 2 and PO 2 values of whole blood.

Basically, such an instrument includes a PO 2 electrode 10 which forms the sensor means for measuring the partial pressure of oxygen in the blood and is associated with circuitry such as amplifiers 11, 13 and 15 designed to produce a signal representative of such partial pressure of oxygen and also includes an analog-to-digital converter l C Oa so that the signal may be converted to digital form to be displayed for easy reading on a suitable display means 102 a The second channel includes a PCO 2 electrode which may be identical to the electrode assembly having the same reference numeral and described in U S Patent No.

3,694,734, note particularly Fig 1 thereof.

Of course, each such electrode assembly is associated with a sample chamber into which the specimen is introduced, as more fully disclosed in said U S Patent Nos.

3,694,734 and 3,672,843 This PCO 2 channel is also associated with its circuitry, including amplifiers 21, 23, 27 and also an anti-log circuit 25 and, also including its analog-to-digital converter l O Ob and digital display means 102 b.

The p H sensor means, as is well known and disclosed in said Patent 3,762,843, basically comprises a p H measuring electrode 30 a and a p H reference electrode b which are disposed in a suitable junction assembly (not shown), such as may be as disclosed in said Patent 3,762,843 This p H sensor means also has its associated circuitry, including amplifiers 31, 33, 35 and an analog-to-digital converter 100 c and its digital display means 102 c.

What has so far been described represents of course the essential and basic elements of a three-channel blood gas analyzer instrument The automatic calibration system of the invention will have to be coupled to each of these three-channels, as now more fully described.

The continuous automatic calibration system of the invention includes a memory circuit 40 a, 40 b which may be a 12-bit latch circuit This memory circuit is designed for receiving and storing a reference number which has to be manually dialed in through signal paths 41 a and 41 b It should be noted that the p H channel does not require such a memory circuit since for the purpose of calibrating this channel, the high buffer solution value of 7 834 is used as the constant reference number.

In the blood gas instrument provided with the continuous automatic calibration system, it is required that standard calibrating gases and a p H buffer solution are constantly maintained in the respective measuring chamber except of course when a sample is being analyzed and also following such analysis when the measuring chambers and associated tubes are flushed and cleaned by a flushing solution Hence to activate the continuous automatic calibration system of the invention, the operator first introduces, via signal paths 41 a and 41 b, the reference numbers of the standards which are known to him and are in the respective measuring chambers, into the memory circuits 40 a and 40 b for the respective PO 2 and PCO 2 standards Then he enables these reference numbers as by actuating enable 42, which stores these numbers into these memories They will stay latched-in in these memory circuits until the operator again manually intervenes to change the reference numbers, should he for instance use different standards in the measuring chambers.

These memory circuits are furthermore designed for constantly producing at their respective outputs 44 a and 44 b, a reference signal representative of such reference numbers dialed into these circuits.

These reference signals are also designated with the capital letter "B" and define one of the inputs to a comparator circuit 50 a, 50 b and 50 c The other input to this comparator circuit is indicated by the capital letter "A" and represents the output of the respective channels of the analytical instruments at 104 a, 104 b and 104 c as taken from the respective analog-to-digital converters l Oa, l O Ob and 10 c.

The comparator circuits are designed to compare the values as represented by "A" and "B" and in instances where "A" is larger than "B", to produce a corresponding output signal on leads 52 a, 52 b or 52 c If on the other hand, the comparator circuit finds the signal "A" is smaller than "B", then it will produce an output on leads 54 a, 54 b or 54 c These respective signals will each connect to AND gates 53 and receive their respective second inputs from a sequencer 272 via lead 274 to enable autocalibration Such a sequencer may be designed as more fully described in the above mentioned U S Patent No.

3,672,843.

In instances where the comparator circuit finds that signal "A" is larger than signal "B" and upon the receipt of the enable signal via lead 274, the respective AND gate 53 will close switch 55 of an RC integratorand-hold circuit 60 a, 60 b or 60 c so as to charge it up positive On the other hand, in instances where the comparator circuit finds that signal "A" is smaller than signal "B" then in like fashion, the other switch 57 is closed so as to charge the integrator-and1,564,981 hold circuit 60 a, 60 b and 60 c negative through a common respective input 58 a or 58 b or 58 c.

Such an RC integrator-and-hold circuit is more fully shown in Fig 2 a Switches 55 and 57 as well as the third switch indicated as at 53 are preferably each solid state switches and are well-known to those skilled in the art Switch 55 connects one input of operational amplifier 64 via lead 58 and across resistor RI to a positive d c voltage + 0.5 v, while switch 57 connects the same input of operational amplifier 64 across resistor R 2 to a negative d c voltage of -0 5 v The other input of operational amplifier is grounded It should also be noted that this RC integrator and-hold circuit is powered by internal power supply voltages representing the other two inputs to operational amplifier 64 and that these d.c voltages are + 12 v and -12 v respectively.

In the feedback loop of this operation amplifier 64 is connected a capacitor marked Cl and in parallel therewith, a resistor R 3 and the previously mentioned third switch 53 which is normally open and may be closed by a second reference enable signal coupled thereto via lead 43, as will be more fully described below The output of the RC integrator-and-hold circuit is indicated as at 62 and is across output resistor R 4.

The respective values for the operative components of these resistors vary, depending upon in which channel the calibration is being utilized, as more fully given in Fig 2 b.

As may be seen in Fig I the output 62 a of the integrator-and-hold circuit 60 a is coupled to amplifier 13 so, as to affect its gain, i e, "SLOPE" control since this is the PO 2 channel In the other two channels, outputs 62 b and 62 c of the sample-and-hold circuits 60 b and 60 c are coupled to amplifiers 23 and 33 respectively and more specifically to their BALANCE, i e, offset controls.

With particular reference to Fig 4 of above referred to U S Patent No 3,642,843, it should be noted that the output 62 a of the integrator-and-hold circuit 60 a would be coupled to SLOPE 114 in the PO 2 channel.

The ouput 62 b would on the other hand be connected to the lead marked BALANCE therein, while the output 62 c would be connected in the p H channel to the lead marked BALANCE 106 Of course, the respective inputs "A" from the analog-todigital converters 100 a, 100 b, 100 c to the comparator circuits 50 a, 50 b, 50 c would be derived from the respective digital display means, 100, 102 and 104 as shown in said Fig 4 of said Patent 3,764,843.

By way of another example and this time using Fig I of above referenced Patent 3,694,734, which of course shows only the PCO, channel, the instrument output "A" would be taken from the analog-to-digital converter 100, while the output of the automatic calibration system of the present invention 62 b would be coupled to the connection between capacitor 74 and resistor 92 so as to influence the input of operational amplifier 76 in said Fig 1.

Most common deviations in instrument readings occasioned by small shifts in readings, slow response or system noises will be corrected by the application of the input signals from these RC integrator-and-hold circuits coupled, as above described, to their respective channel amplifiers 13, 23 or 33 There may, however, be instances where for one reason or another the error is of such a magnitude as to be beyond the maximum allowed correction range of the integrator-and-hold circuit In such instances the comparator circuit will keep on detecting the differences between signals "A" and "B" and produce a further output signal on output leads 56 a, 56 b or 56 c The signals therefrom are passed through a suitable delay means which may be a one second delay means 66 a, 66 b or 66 c, and via a AND gate 68 a, 68 b or 68 c to an error circuit 70 a, 70 b or 70 c The sequencer 272 at the appropriate time enables these error circuits via lead 276 When that occurs, the particular measuring channel of the instrument will be disabled by suitable means, not shown, well-known to persons skilled in the art One such means may be that the respective display 102 a or 102 b or 102 c will commence flashing, indicating error and requiring the operator's intervention to correct Such an error may be occasioned for example by a defective electrode or a broken membrane for such electrode or large and persistant system noise or rather slow instrument response.

One limitation of the correction range of the integrator-and-hold circuits is represented by the internal power supply voltages d c + 12 v and d c -12 v, driving the integrator-and-hold circuit, as shown in Fig.

2 a The second limitation arises from the R.C time constant (Rl-Cl or R 2-Cl) of the integrator-and-hold circuit and of course from the specific values of these resistors, as shown in Fig 2 b, depending on what channel they happen to be incorporated.

Following a major malfunction in the analytical instrument such as requiring for instance the replacement of a defective electrode, the operator may wish to introduce new reference numbers into the memory circuits 40 a, 40 b To do so, he has to adjust the instrument back to zero This is accomplished by closing switch 53 1,564,981 5 appearing in the feedback loop of the operational amplifier 64 of the sample-andhold circuit as shown in Fig 2 a via a signal transmitted over lead 43 At the same time, the memory circuit enable over lead 42 in Fig I will be interrupted Following correction of the malfunction as by the replacement of the defective electrode, calibration standard is introduced into the measuring chamber in contact with the new electrode and the new reference number from that calibration standard is manually dialed in once again into the respective memory circuit 40 a, 40 b via leads 41 a, 41 b.

With the new reference numbers in the memory circuit, the same is enabled via lead 42 and at the same time switch 53 is moved to its normally open position.

Fig 3 depicts the timing diagram of the continuous automatic calibration system of this invention The uppermost horizontal line represents the value of the reference number "B" as appearing on output 44 a or 44 b of the respective memory circuit or as the representative of the constant reference number appearing on lead 44 c Below this and for a shorter period, appears the next horizontal line representative of the instrument's output of a particular measuring channel and shown as "A" The distance between these lines is representative of the difference between "A" and "B" as they are seen by the particular comparator circuit 50 a, 50 b or 50 c.

Assuming that the instrument has just completed a previous analysis followed by rinsing of the measuring chambers and tubes by flush solution, the instrument automatically introduces respective calibration standards into the measuring chambers, as exemplified by Time I in the drawing in Fig 3 This is followed by the sequencer 272 allowing a certain time period for the instrument to achieve equilibration with the just introduced calibration standard This time period is represented by Time II in Fig 3.

A normally functioning analytical instrument will during this period, adjust the output of its analog-to-digital converter to read exactly the same value as the reference number, thus not requiring any intervention at all by the automatic calibration system of the invention This is represented by the curve marked "normal response " Should the measuring channel output "A" not reach the level of what it should be during this equilibration period for any reason, then at the expiration of this equilibration time period, the sequencer 272 via lead 274, as previously described with reference to Fig I now enables the autocalibration system of the invention to permit it to attempt instrument readout correction.

This auto-calibration occurs during the time period shown as Time III in Fig 3 If the error to be corrected is within the capability and within the maximum correction range of the integrator-and-hold circuit, then the output of the instrument at the respective analog-to-digital converter will once again equal the reference numbers.

In cases, however, where the malfunction is of such magnitude as to be beyond the capability of the system of the invention to correct, the sequencer 272 will then enable the error circuits 70 a, 70 b, 70 c via lead 276 as previously described and keep it enabled during the time period shown as time IV in Fig 3 If at this point the instrument signal output "A" still not equals the reference signal "B" as seen by the comparator circuit a, or 50 b or 50 c, the signal representative of the difference therebetween will be passed through a suitable delay means such as the one second delay 66 a, 66 b or 66 c, and combined with the error enable signal, will actuate the error circuit 70 a, 70 b or 70 c.

This will then start the instrument display 102 a, 102 b or 102 c flashing Consequently, the operator will be warned of instrument malfunction, requiring his intervention.

Thus, there has been described a continuous automatic calibration system and method of an analytical instrument which system is designed to work through constant measurement of a calibration standard and the continuous calibration of instrument output data to previously dialed in reference numbers More particularly, the system has been described with reference to a three-channel blood gas instrument It should be understood that other like analytical instruments may be equally provided with the continuous calibration feature disclosed herein At the same time, the system also automatically indicates instrument malfunction without requiring any additional specific circuitry.

Thus, the system allows for continuous and automatic corrections of minor system errors caused by transient noises, shifts in reading and slow response, and it will indicate any major instrument malfunction in a manner to warn the operator that his intervention is required.

Claims (13)

WHAT WE CLAIM IS:-

1 An analytical instrument for measuring constituents of a fluid sample, comprising, at least one sensor means, first circuitry producing a signal representative of the constituent sensed by said sensor and including an analog-to-digital converter for converting said signal to for display, and means digital form for providing continuous calibration of the instrument except when sampling, by means of a second circuitry including, a comparator circuit 1,564,981 6 I 5649 R 1; continuously comparing the output signal of said analog-to-digital converter to a reference signal and producing an output signal representative of the difference resulting from said comparison, and an RC integrator-and-hold circuit connected to the output of said comparator circuit and producing in turn a compensatory voltage coupled to said first circuitry.

2 The analytical instrument of Claim 1 in which said reference signal is continuously produced by a memory means in response to previously stored reference information therein.

3 The analytical instrument of Claim 1, including an error display means activated by said comparator circuit when said difference between said instrument output and said reference signal exceeds the maximum allowed correction range of said integrator-and-hold circuit as determined by its R-C time constant.

4 The analytical instrument of Claim 3 also having a delay means interconnected between said comparator circuit and said error display means.

An analytical instrument for measuring constituents of a fluid sample, comprising at least one sensor means, first circuitry producing a signal representative of the constituent sensed by said sensor and including an analog-to-digital converter for converting said signal to digital form for display, and means for providing continuous calibration of the instrument except when sampling, by means of a second circuitry, including a memory means receiving and storing reference information and producing at its output a reference signal representative of said information, a comparator circuit having one input receiving said reference signal and a second input connected to the output of said analog-to-digital converter and producing at its output a signal representative of the difference therebetween, an RC integrator-and-hold circuit having an input and an output, with its said input coupled to said comparator circuit output and producing in response thereto a compensatory voltage at its said output which in turn is coupled to said first circuitry to correct for errors in said signal representative of said constituent.

6 The analytical instrument of Claim 5, including an error display means coupled via a delay means to the output of said comparator circuit for displaying an error when said difference between the instrument output and said reference signal exceeds the R-C time constant of said integrator-and-hold circuit for a period in excess of a pre-determined time.

7 A method of calibrating with calibration fluid an analytical instrument useful for measuring constituents of a fluid sample and having circuitry for producing and displaying a signal represenative of such constituents, comprising, continuously comparing, except when sampling, the output of said instrument to a reference signal, applying the difference resulting from said comparison to charge or discharge an RC integrator-and-hold circuit, and coupling the resultant output from said integrator-and-hold circuit to said instrument circuitry continuously to adjust its signal output.

8 The method of Claim 7 further including constantly measuring calibration standards except when a sample is presented to the instrument for measurement.

9 The method of Claim 7 in which when said difference between instrument output and said reference signal is such as to be beyond the capability of said integratorand-hold circuit to correct, producing an error signal for warning an operator.

The method of Claim 7, in which said error signal is produced following the elapse of a pre-determined time period.

11 A method of maintaining an analytical instrument useful for measuring constituents of a fluid and having circuitry for producing and displaying a signal representative of such constituents constantly in immediate operating condition comprising measuring continuously, except when sampling, calibration standards, comparing continuously, except when sampling, the output of said instrument to a reference signal, applying continuously the difference between said output and said reference signal to charge or discharge an RC integrator-and-hold circuit, coupling continuously, the output of said integrator-and-hold circuit to said instrument circuitry continuously to correct its signal display, and producing an error signal for warning an operator when said difference between said output and said reference signal is beyond 1 564981 r 1,564,

981 the capability of said integrator-and-hold circuit to correct.

12 The method of claim 11, in which said error signal is produced following the elapse of a pre-determined time period.

13 The method of Claim 11, in which said reference signal has been stored in a memory means of said instrument.

POTTS KERR & CO, Chartered Patent Agents, 27, Sheet Street, Windsor, Berkshire SL 4 IBY.

and 15, Hamilton Square, Birkenhead, Merseyside, L 41 6 BR.

Printed for Her Maiesty's Stationery Office, by the Courier Press, Leamington Spa 1980 Published by The Patent Office 25 Southampton Buildings London WC 2 A l AY, from which copies may he obtained.